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βIVΣ1 spectrin stabilizes the nodes of Ranvier and axon initial segments

Saltatory electric conduction requires clustered voltage-gated sodium channels (VGSCs) at axon initial segments (AIS) and nodes of Ranvier (NR). A dense membrane undercoat is present at these sites, which is thought to be key for the focal accumulation of channels. Here, we prove that βIVΣ1 spectrin...

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Autores principales: Lacas-Gervais, Sandra, Guo, Jun, Strenzke, Nicola, Scarfone, Eric, Kolpe, Melanie, Jahkel, Monika, De Camilli, Pietro, Moser, Tobias, Rasband, Matthew N., Solimena, Michele
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172023/
https://www.ncbi.nlm.nih.gov/pubmed/15381686
http://dx.doi.org/10.1083/jcb.200408007
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author Lacas-Gervais, Sandra
Guo, Jun
Strenzke, Nicola
Scarfone, Eric
Kolpe, Melanie
Jahkel, Monika
De Camilli, Pietro
Moser, Tobias
Rasband, Matthew N.
Solimena, Michele
author_facet Lacas-Gervais, Sandra
Guo, Jun
Strenzke, Nicola
Scarfone, Eric
Kolpe, Melanie
Jahkel, Monika
De Camilli, Pietro
Moser, Tobias
Rasband, Matthew N.
Solimena, Michele
author_sort Lacas-Gervais, Sandra
collection PubMed
description Saltatory electric conduction requires clustered voltage-gated sodium channels (VGSCs) at axon initial segments (AIS) and nodes of Ranvier (NR). A dense membrane undercoat is present at these sites, which is thought to be key for the focal accumulation of channels. Here, we prove that βIVΣ1 spectrin, the only βIV spectrin with an actin-binding domain, is an essential component of this coat. Specifically, βIVΣ1 coexists with βIVΣ6 at both AIS and NR, being the predominant spectrin at AIS. Removal of βIVΣ1 alone causes the disappearance of the nodal coat, an increased diameter of the NR, and the presence of dilations filled with organelles. Moreover, in myelinated cochlear afferent fibers, VGSC and ankyrin G clusters appear fragmented. These ultrastructural changes can explain the motor and auditory neuropathies present in βIVΣ1 −/− mice and point to the βIVΣ1 spectrin isoform as a master-stabilizing factor of AIS/NR membranes.
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spelling pubmed-21720232008-03-05 βIVΣ1 spectrin stabilizes the nodes of Ranvier and axon initial segments Lacas-Gervais, Sandra Guo, Jun Strenzke, Nicola Scarfone, Eric Kolpe, Melanie Jahkel, Monika De Camilli, Pietro Moser, Tobias Rasband, Matthew N. Solimena, Michele J Cell Biol Research Articles Saltatory electric conduction requires clustered voltage-gated sodium channels (VGSCs) at axon initial segments (AIS) and nodes of Ranvier (NR). A dense membrane undercoat is present at these sites, which is thought to be key for the focal accumulation of channels. Here, we prove that βIVΣ1 spectrin, the only βIV spectrin with an actin-binding domain, is an essential component of this coat. Specifically, βIVΣ1 coexists with βIVΣ6 at both AIS and NR, being the predominant spectrin at AIS. Removal of βIVΣ1 alone causes the disappearance of the nodal coat, an increased diameter of the NR, and the presence of dilations filled with organelles. Moreover, in myelinated cochlear afferent fibers, VGSC and ankyrin G clusters appear fragmented. These ultrastructural changes can explain the motor and auditory neuropathies present in βIVΣ1 −/− mice and point to the βIVΣ1 spectrin isoform as a master-stabilizing factor of AIS/NR membranes. The Rockefeller University Press 2004-09-27 /pmc/articles/PMC2172023/ /pubmed/15381686 http://dx.doi.org/10.1083/jcb.200408007 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Lacas-Gervais, Sandra
Guo, Jun
Strenzke, Nicola
Scarfone, Eric
Kolpe, Melanie
Jahkel, Monika
De Camilli, Pietro
Moser, Tobias
Rasband, Matthew N.
Solimena, Michele
βIVΣ1 spectrin stabilizes the nodes of Ranvier and axon initial segments
title βIVΣ1 spectrin stabilizes the nodes of Ranvier and axon initial segments
title_full βIVΣ1 spectrin stabilizes the nodes of Ranvier and axon initial segments
title_fullStr βIVΣ1 spectrin stabilizes the nodes of Ranvier and axon initial segments
title_full_unstemmed βIVΣ1 spectrin stabilizes the nodes of Ranvier and axon initial segments
title_short βIVΣ1 spectrin stabilizes the nodes of Ranvier and axon initial segments
title_sort βivσ1 spectrin stabilizes the nodes of ranvier and axon initial segments
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172023/
https://www.ncbi.nlm.nih.gov/pubmed/15381686
http://dx.doi.org/10.1083/jcb.200408007
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